VIRAL DETERMINANTS OF PATHOGENESIS BY FELVS AND HTLV-I

逆转录病毒能够诱导消融以及增殖 淋巴网状系统疾病。 诱导t细胞 猫白血病/淋巴瘤与A亚群感染相关， B猫白血病病毒（FeLV）和I型感染的人类 人T细胞嗜酸性病毒（HTLV-I）。 相反，亚组C FeLV 会导致猫的再生障碍性贫血，HTLV-III可能是导致 艾滋病在人类 因为FeLV和HTLV诱导的疾病谱 如此相似，FeLV被认为是最合适的动物模型 用于病毒相关的人类恶性肿瘤和艾滋病。 我建议分子和 FeLV A、B和C以及HTLV-I原型病毒的生物学分析， 定义其生物活性和遗传的关键方面， 决定这些属性的特征。 分子研究将包括 转录分析、分子克隆和DNA序列测定 病毒分离株和重组FeLV和FeLV/HTLV的生成 克隆DNA的体外操作。 生物学研究将包括 转染和转录活性、病毒产生和 在幼稚大鼠胚胎转化中补充癌基因的能力 成纤维细胞 通过转染衍生的某些病毒也将被 接种到家猫中以监测致病活性。

Retroviruses are capable of inducing ablative as well as proliferative diseases of the lymphoreticular system. Induction of T-cell leukemia/lymphoma is associated in cats with infection with subgroups A and B Feline Leukemia Viruses (FeLV), and in humans with infection with Type I Human T-cell Lymphotrophic Viruses (HTLV-I). In contrast, subgroup C FeLVs will induce aplastic anemia in cats, and HTLV-III is the probable cause of AIDS in humans. Because the spectrum of disease induced by FeLV and HTLV is so similar, FeLV is considered to be the most appropriate animal model for virus-associated human malignancy and AIDS. I propose molecular and biological analyses of FeLV A, B and C and HTLV-I prototype viruses to define crucial aspects of their biological activity and the genetic features which determine these properties. Molecular studies will include transcription analysis, molecular cloning and DNA sequencing of natural virus isolates and generation of recombinent FeLV and FeLV/HTLV following in-vitro manipulation of cloned DNAs. Biological studies will include transfection and tests for transcriptional activity, virus production and ability to complement oncogenes in transformation of naive rat embryo fibroblasts. Certain viruses derived by transfection will also be inoculated into domestic cats to monitor pathogenic activity.